The mechanisms by which the human brain assembles and maintains a network of over a billion neurons remains a fundamental question in neuroscience. The mouse olfactory system, with its accessible and relatively large olfactory tissue and pool of constantly overturning sensory neurons (OSNs) offers a unique model to examine this question. Our long time goal is to understand the mechanisms involved in the establishing and maintaining the neuronal connections between the main olfactory epithelium and the main olfactory bulb. Recent findings have linked major histocompatibility type I (MHCI) molecules and the MHCI signaling pathway to neuronal restructuring and refinement. We hypothesize that MHCI molecules play a role in OSN axonal guidance to the MOB. This hypothesis is based on our preliminary findings that (1) MHCI molecules can be detected in the glomerular layer of the main olfactory bulb, and (2) there are OSN targeting and glomerular anomalies in MHCI-deficient mice. Our specific aims are:(1) Characterize and localize the expression pattern of MHCI molecules in the mouse olfactory system. (2) Correlate a deficiency in cell surface class I MHC expression with an increase in OSN mistargeting and an alteration of the organization of the glomerular layer of the MOB.